Cancer is one of the most common diseases in the world, and treatments that are currently being performed are surgery, radiotherapy, and chemotherapy. Although molecular mechanisms of cancer have been actively studied, many of the currently developed therapies rely on surgical procedures. Recently, however, a variety of targeted therapeutic agents, such as a small molecule inhibitor, a monoclonal antibody, and a short tumor cell-targeting peptide, have been developed and used as therapeutic agents (Corti A et al., Blood. 2008; 112:2628-35). In particular, a short targeting peptide is highly permeable to a tissues and has low toxicity and immune responses, making them highly effective as an effective anticancer agent (Yang W et al., Clin Cancer Res. 2008; 14:5494-02).
A phage display technique using peptides and proteins is a very useful method of identifying ligands specific to target cells and is a method that has been widely used to discover peptides and proteins that target tumor cells in vitro and in vivo. Representatively, in in vivo phage screening in a phage library of mouse models, RGD, GSL, and NGR motifs are specifically bound to integrin which is activated in epithelial tumors where angiogenesis is activated, VGF receptor, MMP, or the like (Pasqualini R et al., Ann Hematol. 2002; 81: S66-S67), and are found to be expressed in IL11 receptors of prostate blood vessels and microvessels of breast cancer (Arap W et al., Proc. Natl. Acad. Sci. USA. 2002; 1527-31). However, these study results do not provide a phage that can selectively identify patterns appearing transiently at the stage where early tumors are progressed to malignant tumors. Therefore, there is a need to develop peptides and proteins that targets what is specifically expressed at each stage of tumor cells.
A drug system or target therapy that delivers a drug selectively to a tumor has attracted a great deal of attention, because use of the same amount of anticancer drugs can increase the efficacy of the drug, and at the same time, can significantly reduce side effects on normal tissues. In addition, when applied to the gene therapy, virus can be selectively delivered to tumor cells, so as to increase treatment efficiency and reduce serious side effects. To date, antigens that are specific to tumor cells and antibodies that target the antigens have been mainly developed. However, in case of antibodies, there are problems such as concerns of immune response and low efficiency of penetration into tissues. In case of peptides, small molecular weights thereof reduce concerns of immune response and there are advantages of easy transmission into tissues. Therefore, when linking cancer-targeting peptides to existing anticancer drugs, such cancer-targeting peptides can be utilized as drug delivering materials that delivers a drug selectively to tumor. In this regard, there is a need to develop a cancer-targeting peptide.